Summary Our project brings together the large NewYork-Presbyterian (NYP) health system with its affiliated Medical Centers ? Weill Cornell Medicine (WCM) and the Columbia University Medical Center (CUMC), as well as the CUMC partner, Harlem Hospital (HH), a community-based public health facility, to achieve the aims of the national Precision Medicine Initiative (PMI). We will leverage our pre-existing Hospital Network Infrastructure to enroll at least 150,000 patients over 5 years from our ethnically diverse New York City population into a cohort named the NYC Precision Medicine Initiative cohort (NYC-PMI). We will collect and pre-process appropriate biospecimens from all participants including blood sample, saliva sample, and a urine sample. We will extract all electronic health record data for our participants, and provide standardized physical exam, survey data and all other phenotypic data as required for the national cohort to ensure harmonization with PMI data standards. Our HPO will also perform real-time epidemiological modeling of the characteristics of the participants enrolled and adjust enrollment to meet the goals of the National Cohort. Finally, we will actively engage community members, leaders, and organizations throughout New York City to ensure that the aims of the National PMI are appreciated by the broader community and that participants understand the initiative, its benefits and the importance of remaining engaged through their lifespan. We will bring into the national study a demographically diverse cohort that will feature a broad range of rare and common clinical disorders for which we provide expert care at our HPO. Thus, we will not only enroll the requisite number of participants and contribute diversity to the national cohort, but we will provide the clinical and research expertise necessary to make effective use of genomic data. We have long-standing experience with community engagement in research, and have long-standing experience collaboratively in cooperative NIH grant activities to ensure that the overall scientific aims of the PMI are achieved.